Brief description of study

Electroconvulsive therapy (ECT) has unparalleled efficacy in treating severe depression, and
is also useful in treatment-refractory cases of schizophrenia and obsessive compulsive
disorder (OCD). However, its use is limited by significant adverse effects on memory and
cognition. In addition, ECT cannot be precisely targeted, since it relies on unpredictable
pathways of electrical conduction through the brain. Magnetic seizure therapy (MST) is
currently under investigation as a targetable, cognition-sparing alternative to ECT. MST uses
magnetic fields rather than electrical stimuli for seizure induction, dramatically reducing
the passage of induced current through undesired brain regions. 10 years of experimental
studies have established the safety of MST in animal and human subjects. This pilot study
will investigate whether MST has similar efficacy to ECT, with fewer cognitive side effects,
in patients with severe depression, schizophrenia, and OCD.

Detailed Study Description

Although ECT is effective against severe depression, psychosis, and OCD, it also produces
significant impairments of autobiographical memory and other cognitive functions. These side
effects limit the acceptability and tolerability of ECT in many patient populations. They
also limit the number of treatments that can be administered in a course of ECT, leading to
high relapse rates once ECT is discontinued. In animal studies, MST has been shown to have
far fewer adverse cognitive effects than ECT. In small human studies, humans have shown
faster subjective and objective recovery of orientation after MST than with ECT. However, the
precise degree of cognitive sparing in MST versus ECT has yet to be established. Likewise,
the comparative efficacy of MST versus ECT in severe depression, schizophrenia, and OCD
remains to be seen. The investigators aim to determine whether MST spares autobiographical
memory and other cognitive functions, while retaining comparable efficacy to that of ECT.

Objective 1: To compare the efficacy of MST and ECT in treating patients with severe
depression, schizophrenia, and OCD.

Hypothesis 1: MST will have equivalent efficacy to ECT on objective measures of mood,
schizophrenia, and OCD symptoms.

Objective 2: To compare the effects of MST and ECT on autobiographical memory and other
cognitive functions in patients with severe depression, schizophrenia, schizoaffective
disorder and OCD.

Hypothesis 2: MST will have significantly lower adverse effects on objective measures of
autobiographical memory and other cognitive functions in patients with severe depression,
schizophrenia, and OCD.

Objective 3: To compare the changes in brain function that result from MST and ECT.

Hypothesis 3: Both MST and ECT will produce changes in functional brain activity consistent
with antidepressant response, antipsychotic response, and antiobsessive response, along with
a sparing of cognitive functions.

The discovery of a viable alternative to ECT, with equivalent efficacy but fewer side
effects, would have a transformative effect on the treatment of several forms of severe
mental illness. At present, many patients who could benefit from ECT do not pursue this
treatment due to concerns about cognitive side effects, as well as the enduring social stigma
of ECT itself. In addition, many patients who have benefited from ECT are obliged to
discontinue this effective treatment because of mounting cognitive side effects; high rates
of relapse then ensue.

If MST could be shown to spare autobiographical memory and other forms of cognition, many
more patients would be willing to take advantage of the treatment. They would also be able to
continue the treatment, when effective, for longer periods. The potential result would be a
dramatic improvement in the rates of remission and relapse for patients with severe
depression and other forms of mental illness.